The cues that distinguish embryo from extra-embryonic tissue

Colour-coded fateCredit: EMBL/Y. Ohnishi

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In your beginning, there were cells. A clump of cells, each unique, but all variations on a theme. And yet, some of those cells developed into your body, while others became the placenta and accompanying tissues that supported you in the womb. But according to scientists at EMBL Heidelberg, the fate of each cell isn’t sealed at the start.

Just as children in a classroom will have a range of likes and abilities that may lead them to pursue different careers as they grow up, the embryo has cells with genes that are active at different levels. And just as classmates can influence career choices, cells with particular combinations of genes turned on can influence which genes are on or off in their neighbours. Starting with random variation, cells gradually change until they split into the two populations that will become either the body or ‘extra-embryonic’ tissues. This is what Takashi Hiiragi and colleagues posit, based on their work with mouse embryos.

In a study published in Nature Cell Biology, Yusuke Ohnishi, a postdoctoral fellow in Takashi’s lab, measured the activity of all the genes in each individual cell at different stages of development. The developmental biologists then turned to Wolfgang Huber’s mathematical expertise to compare those cells. “Wolfgang did a statistical analysis to see if we could identify different populations of cells in the early, 32-cell embryo, and the answer was ‘no’,” says Takashi. But just over a day later, when the embryo has grown to more than 150 cells, it is clear that there is one type of cell on the surface and another inside, with marked differences in gene activity. “So then we looked back, to see when was the first point in time where we could identify those two populations, and what made them different,” he explains.

The scientists found that, by the time a mouse embryo has 64 cells, it becomes apparent which of those cells will likely give rise to the animal’s body, and which will contribute to extra-embryonic tissue. At that point, and even though the cells haven’t moved to their final destinations in the embryo, their genetic signatures give them away. There are particular groups of genes that are either turned on or off, depending on what a cell is going to become. “Some of those genes are involved in cell-to-cell communication,” adds Takashi, “Which leads us to think that there’s a ripple effect, where cells influence each other and get pushed further and further down one ‘career’ path.”

Takashi and his group now plan to probe deeper, to study just how the different genes act to take the embryo from an undefined mass to a functioning body complete with supporting tissues.